Burger HG. Diagnostic role of follicle-stimulating hormone (FSH) measurements during the menopausal transition—an analysis of FSH, oestradiol and inhibin. Eur J Endocrinol 1994;130:38–42. ISSN 0804–4643 This review examines the role of follicle-stimulating hormone (FSH) measurement in assessing the significance of symptoms and possible continuing fertility during the menopausal transition. Follicle-stimulating hormone measurement is advocated frequently as a useful diagnostic tool in perimenopausal patients. Several investigators have shown that the serum FSH level increases in the early—midfollicular and early postovulatory phases in women over the age of 40 years who continue to experience regular menstrual cycles. The serum oestradiol level may fall (although this is controversial) and the immunoreactive inhibin level falls, being inversely correlated with the rising FSH level. When alterations in menstrual cyclicity or flow commence, signalling the onset of the menopausal transition, FSH levels may change abruptly, rising into the normal postmenopausal range and falling again into the range normally seen in young fertile women. Oestradiol and inhibin generally fluctuate in parallel with each other but inversely to FSH, although at times oestradiol in particular may be increased markedly. Postmenopausal FSH levels may be followed by endocrine evidence compatible with normal ovulation. After the menopause, FSH levels rise 10–1 5-fold, with low oestradiol and undetectable inhibin levels. It is concluded that FSH measurement is of little value, if any in the assessment of women during the menopausal transition because it cannot be interpreted reliably and because, apparently, ovulatory (and, presumably, potentially fertile) cycles may occur subsequent to the observation of postmenopausal FSH levels. Both oestradiol and inhibin are important negative feedback regulators of circulating FSH. Henry G Burger, Prince Henry's Institute of Medical Research, PO Box 152, Clayton, Victoria 3168, Australia
SUMMARY The rise in plasma testosterone levels following stimulation with human chorionic gonadotrophin (3000 i.u./day for 4 days) has been used as a test of interstitial cell function in normal men and men with testicular disorders. The large majority of patients with testicular disorders resulting in infertility, showed a subnormal testosterone response to stimulation. The most marked impairment was noted in those patients with the biopsy appearance of germinal cell arrest and Sertoli cell only syndrome.
We have identified a group of women with infertility and regular menses who have persistently raised FSH levels and probable incipient ovarian failure (IOF). Thirteen such women (19 cycles) had serum samples taken for RIA of LH, FSH, estradiol, and progesterone (P) 3 times a week over 1 menstrual cycle. Sixty infertile women with normal ovulatory cycles (as determined by hormones and ultrasound scan) served as controls. Overall, the FSH was higher (P < 0.01) on all days of the cycle in the IOF group, serum LH was raised on days-14 to-5 before and days 5–11 after the LH surge. There was no difference between estradiol and P levels in the two groups. Ultrasound scanning showed failure of normal ovulation in the IOF group. Inhibin, measured by RIA in 9 cycles in the IOF group was lower (P < 0.01) during the follicular phase than in 43 normal cycles. The highest inhibin level was seen in the luteal phase, as in normal cycles, but levels were still lower (P < 0.01) in the IOF group. Inhibin was inversely correlated with FSH (P < 0.05) during the follicular and luteal phases and was correlated with P during the luteal phase (P < 0.05) in the IOF group. After 3 weeks of suppression (39 cycles) with an estrogenprogestogen preparation in the IOF group, LH and FSH fell to normal values. Ovulation occurred in 22 cycles on withdrawal of suppression in the presence of high FSH levels and low inhibin levels. No pregnancies occurred. These findings are consistent with the suggestion that diminished ovarian inhibin secretion may contribute to the elevated FSH levels of IOF and indicate that ovulation in the rebound cycle after suppression occurs in the presence of high FSH and low inhibin levels. Such cycles, however, still appear to be subfertile.
Background: It has been suggested that some of the symptoms typically attributed to menopause may be more related to premenstrual syndrome (PMS) than menopause, as perimenopausal women appear to be more prone to PMS-like symptoms, or at least to tolerate them less well. Objective: The objective of this study was to evaluate the effectiveness of a phytotherapeutic intervention comprising a combination of Hypericum perforatum (St. John's wort) and Vitex agnus-castus (chaste tree/berry) in the management of PMS-like symptoms in perimenopausal women. Design: A double-blind, randomized, placebo-controlled parallel trial was conducted over 16 weeks on menopause-related symptoms. Data on PMS-like symptoms were collected at 4-weekly intervals from a small subgroup of late-perimenopausal women (n = 14) participating in this study. The primary endpoint was PMS scores measured on the Abrahams Menstrual Symptoms Questionnaire, comprising the subclusters of PMS-A (anxiety), PMS-D (depression), PMS-H (hydration), and PMS-C (cravings). Herbal combination therapy or placebo tablets were administered twice daily. Results: At the end of the 16-week treatment phase, analyses of covariance showed the herbal combination to be superior to placebo for total PMS-like scores (p = 0.02), PMS-D (p = 0.006), and PMS-C clusters (p = 0.027). The active treatment group also showed significant reductions in the anxiety (p = 0.003) and hydration (p = 0.002) clusters, using paired-samples t tests. Results of trend analyses showed significant treatment group effects across the five phases for total PMS and all subscales, all in the clinically expected direction. No significant trends were evident in the placebo group. Conclusions: These results suggest a potentially significant clinical application for this phytotherapeutic combination in PMS-like symptoms among perimenopausal women. Further research is warranted through a randomized, controlled trial dedicated to investigation of these symptoms.
The binding of 125I-labelled human growth hormone (HGH) to the 'lactogenic' binding sites of rat liver membranes has been shown to be highly dependent on the oestrogen and androgen status of the membranes has been shown to be highly dependent on the oestrogen and androgen status of the animal from which the membranes were prepared. Oestradiol treatment of either male or female rats induced a highly significant rise in HGH binding. The minimum effective dose used was 2-5 mug/day and the rise in HGH binding was apparent after 4 days of treatment. Folowing cessation of oestradiol treatment of male rats HGH binding declined with a half-time of approximately 9 days. In contrast to the stimulatory effect of oestrogen, treatment of female rats with testosterone propionate (minimum effective dose 100-200 mug/day) led to a marked reduction in HGH binding. The influence of both oestrogens and androgens was confirmed following the removal of endogenous sex steroids by adrenalectomy-ovariectomy of female rats and castration of male rats. Scratchard analysis showed that, with the possible exception of adrenalectomy-ovariectomy, all pharmacologically and physiologically induced changes in HGH specific binding reflected changes in binding site capacity; there were no changes in binding affinity. While earlier studies have indicated that the oestrogen effect is primarily indirect and is mediated by the pituitary gland, the mode of action of the androgens is currently unknown. The relatively slow response of HGH binding to hormonal changes would support an indirect action for both the sex steroids. The stimulatory effect of oestrogens and the inhibitory effect of androgens may provide an explanation for the marked sex difference in HGH binding to rat liver membranes.